6th Annual Interdisciplinary Prostate Cancer Congress

Meeting in a Box

Screening for Prostate Cancer – The PSA Controversy

Leonard G. Gomella, MD

US Preventive Services Task Force (USPSTF) Screening Recommendations

• Per the 2012 USPSTF, no healthy man should undergo PSA screening unless symptoms of prostate cancer present

• Full implications have yet to be realized

Moyer VA, Ann Intern Med. 2012;157:120-34.

Task Force:– General physicians– Nurses– Health psychologists– Epidemiologists– Statisticians

Topic assigned by HHS Agency

for Healthcare Research &

Quality

Grade the quality of evidence-

based research

Defined prostate screening as

grade D recommendation

against the service. They had moderate or high certainty that the service has no net benefit or that

the harms outweigh the benefits.

Task Force set up by

congressional mandate in

1984

HHS=US Health & Human Services Department; PSA=prostate-specific antigen.

National Comprehensive Cancer Network (NCCN) Screening

Guidelines• NCCN panelists note the variability in prostate tumor behavior

– Key point is discussion between patient and provider about the risks and benefits of early detection of and treatments for prostate cancer

– Goal is to evaluate aggressiveness of the cancer• Once a patient age 40 starts having risk and benefit discussion about baseline

digital rectal exam (DRE) and absolute PSA values– May annually follow up with DRE and repeat PSA in patients with elevated

PSA (≥1.0 ng/mL), African Americans, men taking 5-alpha-reductase inhibitors

– Testing and biopsy decisions should be individualized for men > age 75 years

• Further timing of follow-ups and DRE and PSA testing dependent on age, and life expectancy– Trying to determine need for TRUS-guided biopsy, and may also use PSA

density, percent-free PSA, and PSA velocity to determine need for biopsy or if cancer is present

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer Early Detection, V2.2012. Accessed Sep 9, 2013.

PSA=prostate-specific antigen; DRE=digital rectal examination; TRUS=transrectal ultrasound.

American Cancer Society (ACS) Screening Guidelines

• ACS supports informed discussion between healthcare provider and asymptomatic men about screening for prostate cancer– Average risk: annually beginning age 50 years with 10+ year life

expectancy– Age 45 if high risk: High risk includes African-American men or

those with first-degree relative with prostate cancer <65 years of age

– Age 40 if very high risk: Very high risk includes multiple family members with prostate cancer at early age

– Include information about uncertainties, risks, and potential benefits• If testing performed, PSA with or without DRE• 2009 guidelines reaffirmed in 2013

Wolf AM, et al. CA Cancer J Clin. 2010;118:244-50.

American Urological Association (AUA) Screening Guidelines

• Recommendations based on age and risk– Average risk:

• < Age 40, not recommended• Age 40-54: do not recommend routine screening• Age 55-69: informed shared decision making about screening

risk and potential benefits• Age 70+ or patients with <10-15 years life expectancy: do not

recommend routine screening– Alternatively, can individualize based on baseline PSA

– High risk: <55 with positive family history or African-American race; decisions should be individualized

• If decision to screen, frequency should be 2+ years instead of annual – Panel believes this will reduce overdiagnoses and false-positives

while maintaining the majority of the benefits

Carter HB et al. J Urol. 2013;190:419-26

PSA-Based Prostate Screening

Potential Benefits• Earlier diagnosis:

– Allows finding cancer at earlier stage, before it is symptomatic, while it is likely localized

– 70% decrease in metastatic disease at diagnosis1

• Relative survival has increased to close to 100% since PSA screening became highly utilized1

– From 1975-1979, 10-year survival was 55.7%

– In 2000, 10-year survival was 98.4%

– US death rates have decreased about 4% per year

Risks and Limitations• Potential for overdiagnosis and

overtreatment in patients with clinically insignificant cancer– Decrease in quality of life,

complications, and cost• Various physiological and pathological

factors can cause a rise in PSA, often temporal

• If PSA detectable, no matter how low, prostate cancer still a possibility2

• Can take time for effect of population-based PSA screening to become significant3

• Though increase in survival of prostate cancer patients, not able to directly link it to PSA-based screening

1. Howlader N et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. http://seer.cancer.gov/csr/1975_2010/. Accessed Sept 2, 2013.

2. Thompson IM et al. N Engl J Med. 2004;350:2239-46. 3. Loeb S et al. J Clin Oncol. 2011;29:464-7.

Implications for Patient Care

• PSA-based screening not appropriate for overall population• Prostate cancer screening makes sense in certain populations

after informed discussion between patient and provider– Patients at high risk for the disease– Patients at high risk for death or morbidity from the disease– Patients in good health with life expectancy > 10-15 years

• Can be difficult deciding treatment versus observation for an individual patient

• Advise patients to seek a second opinion, especially with clinician experienced with both active surveillance and active treatment

Active Surveillance—Current Status and Future

DirectionsE. David Crawford, MD

Watchful Waiting vs Active Surveillance / Active Monitoring

Watchful WaitingActive

Surveillance / Active Monitoring

Primary aim Avoid treatment Individualize management

Patient / tumor characteristicsLimited life

expectancy/ advanced disease

Fit for radical treatment/

localized disease

Treatment timing Delayed Early

Treatment intent Palliative Curative

National Comprehensive Cancer Network (NCCN) Guidelines on Active Surveillance

Recurrence Risk Expected Survival Initial Therapy

Very low risk

< 20 years Active surveillance preferred

≥ 20 years1. Active surveillance

2. Radiotherapy3. Radical prostatectomy

Low risk ≥ 10 years1. Active surveillance

2. Radiotherapy3. Radical prostatectomy

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer, V4.2013. Accessed Sep 1, 2013.

Summary of Active Surveillance Studies

Author N Median Follow-up

(mo)

pT3 in RP Patients

OS CSS

van As - Eur Urol. 326 22 8/18 44% 98 100

Carter - J Urol. 407 41 10/49 20% 98 100

PRIAS 533-1000 48 4/24 17% 90 99

Soloway 99 45 0/2 100 100

Roemeling 278 41 89 100

Khatami 270 63 Not stated 100

Klotz - J Clin Oncol.

452 73 14/24 58% 82 97 @ 10 yr

Total 2130-3000 43 90 99.7

CSS=cancer-specific survival; mo=months; OS=overall survival; p=pathologic; RP=radical prostatectomy.

Active Surveillance: Current Approach

• Offered to all men with Gleason 6, PSA ≤10 (accepted by most)• PSA kinetics a guide only• Confirmatory biopsy within 1 year, targeting

anterior/anterolateral horn• Repeat biopsy every 3-5 years (age, risk tolerance, PSA) to age

80 years• MP-MRI for PSA doubling time < 3 years or volume increase or

3+ minor element 4• Treat if significant Gleason 4 or unequivocal lesion > 1 cm on

MRI

New Endocrine Options for Advanced Prostate Cancer

Robert Dreicer, MD, MS, FACP, FASCO

Abiraterone Phase III Trials: COU-AA-301 and COU-AA-302

301 eligibility criteria:• Progressive mCRPC pts

who failed a docetaxel regimen ± another chemotherapy

302 eligibility criteria:• Progressive chemo-naïve

mCRPC, asymptomatic or mildly symptomatic

Abiraterone 1000mg qd+ prednisone bidRANDOMIZE

(N=1195)2:1

Placebo qd+ prednisone bid

Co-primary endpoints: OS + rPFS by central review

1. de Bono et al. N Engl J Med. 2011;364:1995-2005. 2. Ryan CJ, et al. N Engl J Med. 2013;368:138-48.

1:1(N=1088)

Primary endpoint: OS

Median OS Adverse Events

Abiraterone Placebo Abiraterone

COU-AA-301114.8 mo 10.9 mo Fluid retention and

edema, hypokalemia, cardiac disorders(P < 0.0001)

COU-AA-3022Not reached 27.2 mo Mineralocorticoid-

related + abnormalities on liver-function testing(P = 0.01)

Enzalutamide Phase III AFFIRM Trial

• Median OS: 18.4 mo enzalutamide, 13.6 mo placebo (P < 0.0001)• Adverse events: Enzalutamide group reported 45% of patients with any

≥ grade 3 adverse event vs 53% with placebo– 3% of enzalutamide group and 4% of placebo group had an adverse

event that led to death– Highest reported ≥ grade 3 adverse event was fatigue, with 6% of the

enzalutamide group and 7% of placebo reporting

Eligibility criteria:• CRPC pts who progressed

during or after treatment with a docetaxel-based regimen

Enzalutamide 160 mg qdRANDOMIZE

(N=1199)2:1

Placebo qdPrimary endpoint: OS

Scher HI et al. N Engl J Med. 2012;367:1187-97.mOS=median overall survival.

Second-Line Hormonal Therapy: Remaining Issues

• Optimal timing• Role of combination therapy• When to stop androgen biosynthesis inhibitors

– Major issue in the pre-chemotherapy setting• Optimal dose of steroids for androgen biosynthesis

inhibitors • Issues of divergent practice urology vs oncology

Endocrine Agents in Development

• Lyase inhibitors– Orteronel (TAK 700)– TOK-001 (galeterone)– CFG920– VT-464– EN3356

• Antiandrogens– ODM-201– ARN-509– AZD-3514– EZN-4176– TOK-001 (galeterone)

Evolving Approaches for Chemotherapy for Advanced

Prostate CancerDaniel P. Petrylak, MD

Docetaxel Hormone-Refractory Prostate Cancer

• Docetaxel + prednisone remains the standard of care for first-line chemotherapy for metastatic disease

• Investigating markers for drug resistance

N Randomized Arms Docetaxel Dosage Outcome (mOS in mo)

TAX 3271,2 1006

1. Mitoxantrone + prednisone

2. Weekly docetaxel + prednisone

3. Docetaxel q3w + prednisone

Arm 2: 30 mg/m2/wk 5 on; 1

off * 6 cyclesArm 3: 75 mg/m2

q3wk up to 10 cycles

• Weekly docetaxel had 1.5 mo benefit*

HR Arm 1,2: 0.94, P = 0.14• Docetaxel q3wk had 3

mo benefit*HR Arm 1,3: 0.88, P

=0.005

SWOG 99163 770

1. Mitoxantrone + prednisone

2. Docetaxel + Estramustine +

Dexamethasone

60 mg/m2 d2mOS: Arm 2 had 2 month median survival benefit

HR: 0.80; P = 0.01

1. Tannock et al. N Engl J Med. 2004;351:1502-12. 2. Berthold DR, et al. ASCO Prostate Cancer Symposium 2007; abstract 147. 3. Petrylak et al. New Engl J Med. 2004;351:1513-20.

*Compared to mitoxantrone arm. d2=day 2 of cycle; HR=hazard ratio; mos=months; mOS=median overall survival; pred=prednisone; q=every.

Phase III Trials of Docetaxel Combinations

• To date, no combination improves on docetaxel and prednisone

Docetaxel+Prednisone vs Docetaxel Combined With: Status Results

Bevacizumab Completed Negative

VEGF-Trap (aflibercept) Completed Negative

Atrasentan Completed Negative

ZD4054 Completed Negative

Dasatinib Completed Negative

Lenalidomide Completed Negative

Custirsen (OGX-011) OngoingPending,

completion December 2013

Phase III TROPIC Registration Study of Cabazitaxel vs Mitoxantrone in

Docetaxel-Resistant Patients

• mOS: 12.7 mo mitoxantrone+prednisone, 15.1 mo cabazitaxel+prednisone (P<0.0001)

• Adverse events: Cabazitaxel group reported 8% patients with ≥ grade 3 febrile neutropenia vs 1% in mitoxantrone– Diarrhea was reported in 6.2% of cabazitaxel group and 0.3% of

mitoxantrone group– Leukopenia also higher in cabazitaxel group (68% to 42%)

Eligibility criteria:• mCRPC pts who

progressed during or after treatment with a docetaxel-based regimen

Stratification:• ECOG PS (0, 1 vs 2)• Measurable vs non-

measurable disease

Cabazitaxel q3w + prednisone/prednisolone qd * 10 cyclesR

ANDOMIZE

(N=755)

Mitoxantrone q3w + prednisone/prednisolone qd * 10 cycles

Primary endpoint: OSSecondary endpoints: PFS, response rate, safety

de Bono et al. Lancet. 2010;376:1147-54.

Advances in Immunotherapy

Susan F. Slovin, MD, PhD

Rationale for Immunologic Approaches in Prostate Cancer

1. Well-characterized cell surface molecules: PSA, PSMA, PAP, STEAP, PSCA, Globo H, GM2, MUC-1,2, Tn, TF, Lewisy

2. Biomarkers [PSA, CTCs] to study disease progression/response

3. Widely applicable to all disease states: – Biochemical relapse thru castration-resistant disease

4. Likely potentiated via combinatorial approaches: radiotherapy, chemotherapy, biologic agents (GM-CSF, IL-2) or checkpoint inhibitors (anti-CTLA-4, anti-PD-1), monoclonal antibody-chemo conjugates

Immunotherapies to Date…

Successes (limited)• Sipuleucel-T• Ipilimumab• PROSTVAC• Anti-PD-1

Failures (many)• G-Vax• Protein• Peptide• DNA

Brief Summary of Immunologic Trials in Prostate Cancer

• Sipuleucel-T autologous immunotherapy: Median overall survival benefit 4.1 mo in phase III IMPACT trial (P = 0.03)1

• PROSTVAC-VF vaccine: Primary endpoint of PFS in phase II trial similar with control, but at 3 years median overall survival benefit 8.5 mo (P = 0.006)2

• Ipilimumab antibody to CTLA-4: 10 mg/kg with or without radiotherapy had benefit for patients with tumor-evaluable disease in phase II trial,3 – Ipilimumab is being further tested in 2 phase III trials:

one in chemotherapy-naïve, the other in docetaxel-resistant cases

1. Kantoff PW et al. N Engl J Med. 2010;363:411-22.2. Kantoff PW et al. J Clin Oncol. 2010;28:1099-105. 3. Slovin SF et al. Ann Oncol. 2013;24:1813-21.

Conclusions on Immunologic Approaches in Prostate Cancer

• Not every immunotherapy fits a specific disease and vice versa

• Appropriateness of immune therapy for all clinical states of disease but clinical judgment prevails (ie, potential delay in impact of immune therapy)

• Combinatorial approaches: checkpoint inhibitors alone/together/chemo/RT/vaccines/cytokines

• Monoclonal antibody-chemo conjugates

Novel Therapies and Bone-Targeted Therapy

Daniel P. Petrylak, MD

Skeletal-Related Events in Cancer

• The skeleton is the most common site of metastasis• SRE: fracture, spinal cord compression, radiation or

surgery to bone, and hypercalcemia

Malignancy Site Bone Lesions SREsBreast 65%-75% 68%Prostate 90% 49%Lung 30%-40% 48%Multiple Myeloma 95%-100% 51%

Coleman. Cancer. 1997;80:1588-94. Bubendorf, et al. Hum Pathol. 2000;31:578-83. Saad, et al. Cancer. 2007;110:1860. Coleman. Oncologist. 2004;9:14-27.

SRE=skeletal-related event.

Phase III Trial of Denosumab vs Zoledronic Acid in Castration-Resistant

Prostate Cancer

• Supplemental calcium and vitamin D were strongly recommended

• Primary endpoint: (noninferiority) time to first on-study SRE • Secondary endpoint: superiority

Eligibility criteria:• Hormone-refractory

(castration-resistant)• ≥1 bone metastasisStratification:• Previous SRE• PSA concentration• Chemotherapy for prostate

cancer within 6 wks

Zoledronic acid 4 mg IV + placebo sc q4wk R

ANDOMIZE

(N=1901)

Denosumab 120 mg sc + placebo IV q4wk

IV=intravenous; SC=subcutaneous.

Fizazi et al. Lancet. 2011;377:813-22.

Phase III Trial of Denosumab vs Zoledronic Acid Results

Endpoint Denosumab Zoledronic Acid

HR (95% CI)P Value

Median time to first on-study SRE 20.7 mo 17.1 mo HR=0.82 (0.71-0.95)

P =0.008*

Median TTP 8.4 mo 8.4 mo HR=1.06 (0.95-1.18)P =0.30

Median OS 19.4 mo 19.8 mo HR=1.03 (0.91-1.17)P =0.65

Adverse Event, n (%) P ValueCTCAE grade 3/4 678 (72) 628 (66) 0.01

Hypocalcemia 121 (13) 55 (6) <0.0001

Cumulative ONJ 22 (2) 12 (1) 0.09

*P=0.0002 non-inferiority.CI=confidence interval; CTCAE=common terminology criteria for adverse events;

gr=grade; NR=not reported; TTP=time to progression. Fizazi et al. Lancet. 2011;377:813-22.

FDA-Approved Bone-Targeting Radionuclides for the Treatment of Bone

MetastasesFDA Approval Bone Agent Indication

March 20131 Radium-223

Treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease

March 19972 Samarium-153 lexidronam

Relief of pain in patients with confirmed osteoblastic metastatic

bone lesions that enhance on radionuclide bone scan

June 19933 Strontium-89 Relief of bone pain in patients with painful skeletal metastases

1. Xofigo [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2013. 2. Quadramet [package insert]. Princeton, NJ: EUSA Pharma (USA), Inc.; 2009. 3. Metastron [package insert]. Arlington Heights, IL: Medi-

Physics, Inc.; 1998.

Bone-Targeting Radionuclides for Patients with Prostate Cancer Bone

MetastasesTrial Bone Agent N Results (Improvement Over or vs

Placebo)

Sartor, 2004 phase III

Samarium-153-lexidronam 101 VAS: 2-4 wk (P≤0.05)

PDS: 1-4 wk (P≤0.05)Analgesic use: 3-4 wk (P< 0.03)Placebo 51

Porter, 1993 phase III

Stronium-89 + EBR 126

New painful sites: 0.6 vs 1.2 (P< 0.0002)Analgesic free at 3 mo: 17% vs 2% (P<0.05)Time to further RT: 35 vs 20 wk (P=0.006)Placebo + EBR

Parker, 2013phase III

Radium-223 614 Median OS: 65 vs 49 wk (P <0.001)Median time to first symptomatic skeletal event: 68 vs 43 wk (P <0.001)Placebo 307

ALP=alkaline phosphatase; EBR=external beam irradiation; PDS=pain descriptor scale (nonlinear); RT=radiotherapy; VAS=100-mm pain intensity visual analog scale (linear).

Sartor et al. Urology. 2004;63:940-5. Nilsson et al. Lancet Oncol. 2007;8:587-94. Porter et al. Int J Radiat Oncol Biol Phys. 1993;25:805-13.

Cabozantinib in Bone Metastatic Prostate Cancer

• Phase II Trial1– Cabozantinib administered 100 mg daily– 67% of patients (total N=171) showed bone scan response after

retrospective review– Reduction in bone markers– Other benefits:

• Pain improvement and narcotics reduction• PFS benefit seen regardless of docetaxel pretreatment or naïve • PSA changes discordant with other measures of antitumor activity

• 2nd trial to attempt lower starting doses to limit adverse events2

– Primary outcome was week 6 bone scan response– For N=24 at 40 mg, 1 complete response, 15 partial responses,

8 stable disease with tolerable adverse event profile• Phase IIIs ongoing

1. Smith DC et al. J Clin Oncol. 2013;31:412-19. 2. Lee RJ et al. Clin Cancer Res. 2013;19:3088-94.

Conclusions on Novel Therapies and Bone-Targeted Therapies

• Alpha-emitting isotope therapy improves survival in men with CRPC

• Minimal toxicity• Combination studies with

hormonal/chemotherapeutic agents are underway• New agents are targeting bone and have promising

activity

Can We Combine Novel Agents in the Management of

Advanced Prostate Cancer?Robert Dreicer, MD, MS, FACP, FASCO

Combination Therapy in Metastatic Castration-Resistant Prostate Cancer:

Current Status• Testosterone suppression

– + second-line hormonal therapy– + sipuleucel-T– + docetaxel, + bone-targeted agents– + radiotherapy

Brief Summary of Abiraterone + Enzalutamide Trials in Prostate

Cancer• Phase II MDV3100 in bone metastatic CRPC

(NCT01650194)– N=60, prior chemotherapy allowed

• Proposed Intergroup 3-arm phase III metastatic CRPC– Enzalutamide + abiraterone + prednisone– Enzalutamide monotherapy– Abiraterone + prednisone

CRPC=castration-resistant prostate cancer; Ph=phase.

Combination and/or Sequential Therapy in CRPC: Challenges

• Current reimbursement paradigm is slowly but inexorably coming to an end.

• Compendium listing of drugs will be nice, but will increasingly miss the point.

• In a world of Accountable Care Organizations, medical homes, and contracts for populations, we need to think about VALUE in addition to science/clinical results.

Radium-223 Combination Therapy

• Excellent toxicity profile

• Unique mechanism of action

• Combination studies with androgen receptor-targeted agents

– Issues of other bone-targeted therapy when combined with two potent agents that decrease SREs/impact survival

• Combination with immunomodulatory agents

Near-Term Questions for Combination Therapy

• Can more-potent androgen receptor-targeted therapy cure patients with minimal disease?

– The adjuvant breast paradigm

– Lyase inhibitor + next-generation androgen receptor antagonist

• Locally-advanced prostate cancer status post combined modality therapy

• Cost effective/value-based care questions

Emerging Biomarkers: Ready for Prime Time?

Daniel P. Petrylak, MD

Potential DNA Biomarkers• APC = adenomatosis polyposis coli

– Inactivated in various malignancies including prostate cancer by genetic and epigenetic mechanisms

• GSTP1 = glutathione-S-transferase-P1/π– Believed to play a role in the protection of DNA from oxidative

damage• RASSF1A = Ras association domain family 1 isoform A

– Tumor suppressor• RARβ2 = retinoic acid receptor β2

– Tumor suppressor• MDR1 = multidrug resistance 1

– May play a role in anticancer drug resistance• CCND2 = cyclin D2

– Cell-cycle regulator

PSA Response to CRPC

• While a ≥50% decrease from baseline has been accepted as clinically relevant response,1 a ≥30% decrease has also been demonstrated as a surrogate threshold for predicting survival.2,3

• Record the percentage change from baseline (rise or fall) at 12 weeks, and separately, the maximal change (rise or fall) at any time using a waterfall plot.4

1. Scher HI, et al. J Clin Oncol. 2011;29:3695-704. 2. Petrylak DP, et al. JNCI. 2006;98:516-21. 3. Armstrong AJ, et al. J Clin Oncol. 2007;25:3965-70. 4. Scher HI, et al. J Clin Oncol. 2008;26:1148-59.

PSA Does Not Always Accurately Reflect Response to CRPC Therapy

• Newer therapies, such as sipuleucel-T will improve survival without decreasing PSA levels.

• For cytotoxic or hormonal therapies, early PSA responses, rises or declines, should not be used for clinical decision making.1

– Discordance between PSA change and clinical responses, such as pain response2 or progression/regression of bone metastases, have been reported.3

1. Scher HI, et al. J Clin Oncol. 2008;26:1148-59. 2. Berthold DR, et al. Clin Cancer Res. 2008;14:2763-7. 3. Ryan CJ, et al. Clin Cancer Res. 2011;17:4854-61.

Other Biomarkers With Correlation to Outcomes in Prostate Cancer

Biomarker Population Correlation

Testosterone (T)1,2

Retrospective newly diagnosed bone-only

metastatic treated with LHRH agonist

Correlation of serum T and intraprostatic DHT:• None seen at beginning• Could be observed after 6 mo

neoadjuvant ADT

Circulating tumor cells (CTCs)

CRPC patients receiving chemotherapy3

ORMetastatic CRPC pts on

abiraterone after failing on docetaxel4

• CTCs are useful for predicting treatment response/survival with cytotoxic and hormonal therapies

• However, ~50% of patients do not have detectable CTC levels by current detection methods

• More-ensitive CTC detection techniques needed

1. Perachino M, et al. BJUI. 2010;105:648-51. 2. Nishiyama T, et al. Cancer Res. 2004;10:7121-6. 3. de Bono JS, et al. Clin Cancer Res. 2008;14:6302-9.

ADT=androgen-deprivation therapy; DHT=dihydroxytestosterone; LHRH=luteinizing hormone-releasing hormone

Other Biomarkers With Correlation to Outcomes in Prostate Cancer (cont.)

Biomarker Population Correlation TMPRSS2-ERG fusion1-4

– Rearrangements present ~50% of newly diagnosed patients

– Creates androgen receptor-driven expression of ERG

TMPRSS2-ERG no rearragement, Edel (1 or

2+), and Esplit patient samples

• Exact rearrangement may indicate lethality of tumor2,3

• Association between ERG fusion and PSA decline seen in patients treated with abiraterone4

AR35

– In vitro studies suggest AR3 promotes androgen-independent growth

Patient samples from benign, hormone-naïve, and hormone-resistant

tumors

AR3 appears to be upregulated during prostate cancer progression during hormone therapy, and is associated with androgen-resistant growth

Interleukin (IL)-6Metastatic CRPC6 and

metastatic CRPC receiving first-line docetaxel7

• Higher baseline IL-6 associated with worse prognosis6,7

• Correlation with response to docetaxel7

1. Danila DC, et al. Eur Urol. 2011;60:897-904. 2. Mehra R, et al. Cancer Res. 2008;68:3584-90. 3. Attard G, et al. Oncogene. 2008;27:253-63. 4. Attard G, et al. Cancer Res. 2009;69:2912-8. 5. Guo Z, et al. Cancer Res.

2009;69:2305. 6. George DJ, et al. Clin Cancer Res. 2005;11:1815-20.